The Study On Canine Type 1 Diabetes Mellitus Modle Induced With Alloxan And Its Toxic Effect

The mobility of diabetes mellitus in dogs becomes higher than before. Nearly all diabetes mellitus category in dog is type 1. However, the way to model type 1 diabetes mellitus is immature, and there is little data in this field. Therefore, a further study in this field is blocked. The normal reagent are alloxan and streptozotocin for modeling the canine type 1 diabetes mellitus. Cause of streptozotocin extremely expensive, alloxan was extensively applied to model type 1 diabetes mellitus in mice. No information on the modeling of type 1 diabetes mellitus with alloxan reported. The aims of this experiment were to model canine type 1 diabetes mellitus with alloxan, and evaluate alloxan toxic effect on main organs of dogs.1. Establishment of a model of Canine Type 1 Diabetes MellitusFeed was deprived 12hrs before and 72hrs after dogs were injected with alloxan. Alloxan was injected into vein of 6 adult dogs twice at the dosage of 30mg/kg for inducing type 1 diabetes mellitus, every injection ended in thirty seconds. Blood glucose was detected every two hrs, and the second injection was administrated after blood glucose increased up and stabilized. The fasting blood glucose concentration upto 11.1 mmol/L and lasting two days mean type 1 diabetes mellitus successfully modeled. After that, liver function (including ALT, AST, ALP and CHE), renal function(including CRE and UREA) and pancreatic function (AMY) were analyzed every week. Histopathological character of liver, kidney and pancreas were also observed six weeks later.2.The study on toxic effect of liver, kidney and pancreas caused by alloxanAfter injected, blood glucose increased upto and stabilized on 20mmol/L, and the typical symptom of type 1 diabetes mellitus appeared as polydipsia, polyuria, hyperphagia and emaciation, and etc.3. ResultsAlloxan has an obvious influence on liver function. ALP changed significantly from the first week to sixth week(P<0.01). Although no obvious change(P>0.05)compared with controls in the first three weeks, the biochemical parameters ALT, AST, and CHE changed significantly from the fouth week to sixth week (P<0.01). Obvious influenceon pancreas function was also suggested with serumAMY significantly increased (P<0.01). No obvious influence (P>0.05)on kidney function was detected.Hepatocyte tumefaction, grain denaturalization, vacuolation, focal necrosis, hepatocyte rupture, cell plasm leakage, karyon pyknosis and cataclasm were observed, and piecemeal necrosis appered widely on histopathological slides. Pancreatic acini ruptured and bouncary unclear, and fused. Little panreatic islets and B-cell were observed. No significant pathological changes appeared in kidney.4.ConclusionsAlthough alloxan could damage liver and pancrea severely, no obviously lesion observed in kidney, and extremely the survival rate of dogs in this test was high. The experiment proved that canine type 1 diabetes mellitus model could be successfully induced with 30mg/kg alloxan injected twice. The fasting blood glucose stabilized on 20mmol/L, coming up to the standard of type 1 diabetes mellitus. The canine type 1 diabetes mellitus model firstly induced with multiple injection of low dose of alloxan, which provides a new method and theoretical basisfor ulterior research on canine type 1 diabetes mellitus.